Antibiotic efficacy testing in an ex vivo model of Pseudomonas aeruginosa and Staphylococcus aureus biofilms in the Cystic Fibrosis lung

The effective prescription of antibiotics for the bacterial biofilms present within the lungs of individuals with cystic fibrosis (CF) is limited by a poor correlation between antibiotic susceptibility testing (AST) results using standard diagnostic methods (e.g., broth microdilution, disk diffusion, or Etest) and clinical outcomes after antibiotic treatment. Attempts to improve AST by the use of off-the-shelf biofilm growth platforms show little improvement in results. The limited ability of in vitro biofilm systems to mimic the physicochemical environment of the CF lung and, therefore bacterial physiology and biofilm architecture, also acts as a brake on the discovery of novel therapies for CF infection. Here, we present a protocol to perform AST of CF pathogens grown as mature, in vivo-like biofilms in an ex vivo CF lung model comprised of pig bronchiolar tissue and synthetic CF sputum (ex vivo pig lung, EVPL)

Clinically guided core biopsy and cutaneous punch biopsy in the evaluation of breast lesions:a necessary test or an obsolete skill?

OBJECTIVE: The vast majority of breast cancers are diagnosed via image-guided procedures yet despite significant advances, imaging does not identify all breast malignancies. Clinically suspicious breast lesions with normal breast imaging remain a cause for concern. The aim of this study is to determine the diagnostic value of clinical core and cutaneous punch biopsies in the diagnosis of breast malignancy in clinically suspicious lesions with normal breast imaging. METHODS: All patients with suspicious clinical breast findings and normal imaging who underwent a clinical core and/or cutaneous punch biopsy from 2012 to 2019 were reviewed retrospectively. Patients with subsequent breast malignant diagnosis were analysed. RESULTS: A total of 283 biopsies (166 clinical core, 117 cutaneous punch) performed over the 7-year period were included in the analysis. A total of 263/283 (93%) yielded a benign outcome. A total of 2/283 (0.7%) yielded B3 lesions (probably benign). These lesions were benign on final surgical excision. A total of 18/283 (6.3%) yielded a malignant histopathology. Sixteen out of 18 were cutaneous punch biopsies, and 2/18 were clinical core biopsies. A total of 14/18 patients presented with nipple changes, while 4/18 had a palpable area of concern. Histopathological analysis demonstrated Paget’s disease of the nipple in 8/18, invasive carcinoma in 9/18 out of which two represented a recurrence of breast malignancy. Cutaneous squamous cell carcinoma was diagnosed in 1/18. CONCLUSION: Clinical core and cutaneous punch biopsies remain a valuable tool in the diagnosis of breast cancer particularly in the management of clinically suspicious radiographically occult malignancies

Deepening democracy within Ireland's social partnership

Ireland's social partnership process, now under attack from a number of quarters, has repeatedly been charged with being 'undemocratic' in that it undermines the sovereign position of elected political representatives, with key policy formulation and decision-making taking place in fora outside the institutions of representative democracy. These critiques echo those against new forms of networked governance more globally. A key question therefore is how (and if) democracy may be deepened within social partnership or its potential successor(s). This article addresses this question by employing a post-liberal democratic framework to examine social partnership in practice, and by drawing lessons from another partnership process, Malawi's PRSP. Drawing from Malawi's experience, it is argued that democracy can be deepened within social partnership when governance deliberations and negotiations are conducted under conditions of vibrant public debate and genuine perspective-based representation, and when the communicative and discursive norms are widened to allow for such representation

The role of taxonomic expertise in interpretation of metabarcoding studies

Abstract The performance of DNA metabarcoding approaches for characterizing biodiversity can be influenced by multiple factors. Here, we used morphological assessment of taxa in zooplankton samples to develop a large barcode database and to assess the congruence of taxonomic identification with metabarcoding under different conditions. We analysed taxonomic assignment of metabarcoded samples using two genetic markers (COI, 18S V1–2), two types of clustering into molecular operational taxonomic units (OTUs, ZOTUs), and three methods for taxonomic assignment (RDP Classifier, BLASTn to GenBank, BLASTn to a local barcode database). The local database includes 1042 COI and 1108 18S (SSU) barcode sequences, and we added new high-quality sequences to GenBank for both markers, including 109 contributions at the species level. The number of phyla detected and the number of taxa identified to phylum varied between a genetic marker and among the three methods used for taxonomic assignments. Blasting the metabarcodes to the local database generated multiple unique contributions to identify OTUs and ZOTUs. We argue that a multi-marker approach combined with taxonomic expertise to develop a curated, vouchered, local barcode database increases taxon detection with metabarcoding, and its potential as a tool for zooplankton biodiversity surveys

Point of care detection of SARS-CoV-2 antibodies and neutralisation capacity—lateral flow immunoassay evaluation compared to commercial assay to inform potential role in therapeutic and surveillance practices

IntroductionAs the COVID-19 pandemic moves towards endemic status, testing strategies are being de-escalated. A rapid and effective point of care test (POCT) assessment of SARS-CoV-2 immune responses can inform clinical decision-making and epidemiological monitoring of the disease. This cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers assessed how rapid anti-SARS-CoV-2 antibody testing can be compared to a standard laboratory assay, discusses its effectiveness in neutralisation assessment and its uses into the future of the pandemic.MethodsA point of care lateral flow immunoassay (LFA) detecting anti-SARS-CoV-2 spike (S)-receptor binding domain (RBD) neutralising antibodies (Healgen SARS-CoV-2 neutralising Antibody Rapid Test Cassette) was compared to the Roche Elecsys/-S anti-SARS-CoV-2 antibody assays and an in vitro surrogate neutralisation assay. A correlation between anti-spike (S), anti-nucleocapsid (N) titres, and in vitro neutralisation was also assessed.Results1,777 serology samples were tested using Roche Elecsys/-S anti-SARS-CoV-2 assays to detect total anti-N/S antibodies. 1,562 samples were tested using the POC LFA (including 50 negative controls), and 90 samples were tested using an in vitro ACE2-RBD binding inhibition surrogate neutralisation assay. The POCT demonstrated 97.7% sensitivity, 100% specificity, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 61% in comparison to the commercial assay. Anti-S antibody titres determined by the Roche assay stratified by the POC LFA result groups demonstrated statistically significant differences between the “Positive” and “Negative” LFA groups (p < 0.0001) and the “Weak Positive” and “Positive” LFA groups (p < 0.0001). No statistically significant difference in ACE2-RBD binding inhibition was demonstrated when stratified by the LFA POC results. A positive, statistically significant correlation was demonstrated between the in vitro pseudo-neutralisation assay results and anti-S antibody titres (rho 0.423, p < 0.001) and anti-N antibody titres (rho = 0.55, p < 0.0001).ConclusionHigh sensitivity, specificity, and PPV were demonstrated for the POC LFA for the detection of anti-S-RBD antibodies in comparison to the commercial assay. The LFA was not a reliable determinant of the neutralisation capacity of identified antibodies. POC LFA are useful tools in sero-epidemiology settings, pandemic preparedness and may act as supportive tools in treatment decisions through the rapid identification of anti-Spike antibodies

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Sustainable intensification – “oxymoron” or “third-way”? A systematic review

Sustainable Intensification (SI) is a term that has been advanced to capture a concept that some consider as the ‘third paradigm’ for global agricultural development. However, the term has become subject to intense debates as well as scepticism and confusion regarding its meaning and the characteristics of production systems that could indicate SI (defined as “indicators”). This has resulted in a proliferation of literature. We have conducted a systematic review of a sample of this literature analysing the most commonly suggested indicators of SI in order to investigate the extent to which the critiques of SI are valid in their viewpoints that SI is an oxymoron, underpinned by a productivist agenda, and to identify the critical issues in the development of a comprehensive and unambiguous set of SI indicators. From 633 articles identified by a search of relevant databases, a sample of 75 articles were selected and analysed using the NVIVO™ software. The results were organised according to a Socio-Ecological Systems (SES) framework comprising seven sub-systems or components − resource system, resource units, governance system, resource users, interactions, outcomes, and environment. A total of 218 indicators (both positive and negative) were identified. Most of these indicators focused on the ‘outcomes’ of agricultural systems with the majority being related to agricultural production. Few indicators were identified as relating to the economic and societal dimensions of food systems. Whilst this potentially suggested a productivist bias in the current interpretation of SI it was difficult to draw a black and white conclusion, since for the other system components, the majority of the indicators suggested appeared to take a more holistic point-of-view and emphasised both productivity and sustainability of agricultural systems. Our analysis suggests that a key reason why SI may be viewed with scepticism is a lack of specificity and elucidation of the rationale, scale, and farm type for which SI is proposed. Moreover, a number of the indicators were so loosely defined that the interventions they imply could be enacted without due consideration of the social impacts of their adoption. We conclude that there is need to develop SI indicators according to specific farming types and scales and also with more consideration of the social and political dimensions of food systems in order to promote a constructive dialogue around the concept of SI to take place. Unless the concept of SI is described and measured in such a holistic and inclusive manner, it is unlikely to be accepted as a valid descriptor of sought-after agricultural practices by players in the Third Sector

Extraordinary Biomass-Burning Episode and Impact Winter Triggered by the Younger Dryas Cosmic Impact ∼12,800 Years Ago. 2. Lake, Marine, and Terrestrial Sediments

Part 1 of this study investigated evidence of biomass burning in global ice records, and here we continue to test the hypothesis that an impact event at the Younger Dryas boundary (YDB) caused an anomalously intense episode of biomass burning at ∼12.8 ka on a multicontinental scale (North and South America, Europe, and Asia). Quantitative analyses of charcoal and soot records from 152 lakes, marine cores, and terrestrial sequences reveal a major peak in biomass burning at the Younger Dryas (YD) onset that appears to be the highest during the latest Quaternary. For the Cretaceous-Tertiary boundary (K-Pg) impact event, concentrations of soot were previously utilized to estimate the global amount of biomass burned, and similar measurements suggest that wildfires at the YD onset rapidly consumed ∼10 million km2 of Earth’s surface, or ∼9% of Earth’s biomass, considerably more than for the K-Pg impact. Bayesian analyses and age regressions demonstrate that ages for YDB peaks in charcoal and soot across four continents are synchronous with the ages of an abundance peak in platinum in the Greenland Ice Sheet Project 2 (GISP2) ice core and of the YDB impact event (12,835–12,735 cal BP). Thus, existing evidence indicates that the YDB impact event caused an anomalously large episode of biomass burning, resulting in extensive atmospheric soot/dust loading that triggered an “impact winter.” This, in turn, triggered abrupt YD cooling and other climate changes, reinforced by climatic feedback mechanisms, including Arctic sea ice expansion, rerouting of North American continental runoff, and subsequent ocean circulation changes

Obesity in adults: a 2022 adapted clinical practice guideline for Ireland

This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay